CD19 CAR-T Cell Therapy for Relapsed/Refractory B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia

B-cell Acute Lymphoblastic Leukemia Clinical Trial

Official title:

A Phase I Clinical Trial of Anti-CD19 Chimeric Antigen Receptor With Synthetic Biology Optimizing Nano-vector T Cells Injection for Subjects With Relapsed/Refractory/High-risk B-cell Lymphoma and B-cell Acute Lymphoblastic Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03854994
• Other study ID #: 201707202
• Status: Recruiting
• Phase: Phase 1
• Start date: August 1, 2018
• Est. completion date: August 1, 2022

Study information

• Verified date: February 2019
• Source: Yan'an Affiliated Hospital of Kunming Medical University
• Contact: Peixian Zhang
• Phone: 86-0871-63211268
• Email: px29[@]163.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study is to evaluate the safety and clinical activity of anti-CD19 Chimeric Antigen Receptor T cells (KD-019 CAR-T)infusion in the treatment of relapsed/refractory B-cell Lymphoma and B-cell acute lymphoblastic leukemia （B-ALL）.

Description:

The investigators designed an KD-019 Chimeric Antigen Receptor(CAR) with FMC63 single-chain antibody fragment (Scfv). This CAR has a CD8 hinge and transmembrane domains and a 4-1BB costimulatory domain; T cells expressing this CAR release relatively low levels of cytokines. Subjects with relapsed/refractory CD19-positive B-cell Lymphoma and B-ALL can participate if all eligibility criteria are met. Subjects receive chemotherapy prior to the infusion of KD-019 CAR-T cells. After the infusion, subjects will accept follow-up for side effects and effect of KD-019 CAR-T cells by the sponsor. Study procedures may be performed while hospitalized.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: August 1, 2022
• Est. primary completion date: August 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients or their legal guardians voluntarily participate and sign the Informed Consent Document;

2. 18 Years and older, Male and female;

3. Pathologically and histologically confirmed CD19 + B cell tumors; Patients currently have no effective treatment options, such as chemotherapy or relapse after hematopoietic stem cell transplantation; Or patients voluntarily choose transfusion of anti-CD19 CAR-T cells as the first treatment program;

B-cell tumors / lymphomas and B-cell acute lymphoblastic leukemia include the following four types:

1. B-cell acute lymphoblastic leukemia;

2. Indolent B-cell lymphomas;

3. Aggressive B-cell lymphoma; 4? Subjects:

(1) Residual lesions remain after treatment; (2) Not suitable for Hematopoietic stem cell transplantation (auto/allo-HSCT); (3) Relapse after Complement receptor 1 (CR1) and unsuitable for HSCT; (4) Patients with high risk factors; (5) Relapse or no remission after hematopoietic stem cell transplantation or cell immunotherapy.

5? Have measurable or evaluable tumor foci; 6? Liver, kidney and cardiopulmonary functions meet the following requirements:

1. Serum glutamic pyruvic transaminase (ALT) and serum glutamic oxaloacetic transaminase (AST) <3 ×upper limit of normal (ULN);

2. Total bilirubin =34.2µmol/L;

3. Serum creatinine<220µmol/L;

4. Baseline oxygen saturation=95%;

5. Left ventricular ejection fraction(LVEF)=40%. 7? Subjects who did not receive Chemotherapy, Radiotherapy, Immunotherapy (immunosuppressive drugs) or other treatment within 4 weeks prior to enrollment; Relevant toxicity=1 grade before enrollment (except for low toxicity such as hair loss); 8?Peripheral superficial venous blood flow is smooth, which can meet the needs of intravenous drip; 9?Clinical performance status of eastern cancer cooperation group (ECOG) score =2,Expected survival=3 months;

Exclusion Criteria:

1. Pregnant (urine/blood pregnancy test positive) or lactating women;

2. Planned pregnancy during treatment or within 1 year after treatment, or a male subject whose partner plans pregnancy within 1 year of their cell transfusion;

3. Patients cannot guarantee effective contraception (condom or contraceptives, etc.) within 1 year after enrollment;

4. Active or uncontrollable infection within four weeks prior to enrollment;

5. Patients with active hepatitis B/C;

6. HIV-infected patients;

7. Severe autoimmune or immunodeficiency disorders;

8. Patients are allergic to macromolecule drugs such as antigens or cytokines;

9. Subjects participated in other clinical trials within 6 weeks before enrollment;

10. Systematic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);

11. Mental illness;

12. Drug abuse/addiction;

13. The investigators consider other conditions unsuitable for enrollment.

Related Conditions & MeSH terms

• B Cell Lymphoma
• B-cell Acute Lymphoblastic Leukemia
• Burkitt Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Biological:
• Anti-CD19 CAR-T Cells Injection
Autologous genetically modified anti-CD19 CAR transduced T cells

Locations

Country	Name	City	State
China	Kunming Yan'an Hospital, Oncology Department	Kunming	Yunnan

Sponsors (2)

Lead Sponsor	Collaborator
Yan'an Affiliated Hospital of Kunming Medical University	Nanjing KAEDI Biotechnology Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants with severe cytokine release syndrome(CRS) as a Measure of Safety and Tolerability.	The severe CRS post KD-019 CAR-T cells treatment will be evaluated and the maximum tolerated dose will be determined.	0 to 14 days post infusion
Primary	Copies numbers of CAR in peripheral blood (PB)	Copies numbers of CAR in peripheral blood (PB)	1 year post infusion
Secondary	Overall survival	For all subjects, overall survival refers to the period from being included in the test group to death caused by any reason	2 years post infusion
Secondary	Duration of Response after administration	Duration of Response after administration	2 years post infusion
Secondary	Progress Free Survival after administration	Progress Free Survival after administration	2 years post infusion